Asthma, Genotype
Conditions
Brief summary
This is a study to look at pharmacokinetic levels of different doses of slow release DHEA in subjects with asthma.
Detailed description
Pharmacokinetic (PK) studies of DHEA in asthma have never been done. In many diseases, PK in subjects with disease differs from that of control subjects and those with other conditions. Therefore, researchers are investigating if PK levels of slow release DHEA are different in subjects with asthma who have the HSD3B1 AA or AC phenotypes
Interventions
DHEA is a hormone produced by the body's adrenal gland. In drug form, it is available as an over-the-counter supplement that is available on the market without prescription.
Sponsors
Indiana University
National Heart, Lung, and Blood Institute (NHLBI)
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is an unblinded pharmacokinetic (PK) study to determine optimal dosing for future studies. This study will start with a one-time dose and progress to twice daily dosing for 3 days, every 12 hours. Study cohort will be 9 subjects with asthma. DHEA dose will be 50 mg via slow release capsules. Endpoints will be serum DHEA and DHEA-S levels at 10, 20, 30, 60 min & 2, 4, 6, 8, 12h after administration. After a one-week washout period, the protocol will be repeated using 100 mg of SR-DHEA.
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Adult male or female aged between 18 and 50 at time of enrollment * Evidence of asthma demonstrated by reversibility at visit 0 or by historical methacholine or bronchodilator reversibility if testing was performed under either the 2017 ERS technical standard (22) or the 1999 ATS Guidelines (23) or outside studies, provided that full sets of flow volume loops have been reviewed and approved by the PI. These criteria are defined as one of the following: * For bronchodilator reversibility: An increase in FEV1 ≥10% (24) compared to the baseline (and 200 ml) after up to 8 puffs of albuterol * For historical methacholine responsiveness: Positive methacholine defined as PC20 ≤ 16 mg/ml, or PD20 ≤400 mcg * Physician diagnosis of asthma according to NHLBI guidelines; * Consistent use of an ICS/LABA inhaler for the prior 2 months; * Non smoker; * Females must not be pregnant or lactating; * Absence of non-allergic comorbidities; * Genotype testing positive for either HSD3B1 AA or AC specific variant
Exclusion criteria
* Pregnant or actively trying to become pregnant; breastfeeding * positive urine pregnancy test * Known lung disease other than asthma * Acute (non asthma-related) dyspnea, viral respiratory illness or asthma exacerbation within 4 weeks of screening * Systemic glucocorticoid dosing for maintenance \>10 mg/day of prednisone or equivalent * Patients with significant non-allergic comorbidities (e.g. cerebral palsy, heart disease, kidney disease, liver disease, etc.) * Patients with any know central or peripheral endocrine abnormality such as precocious puberty or diabetes * Patients with any known previous adverse reaction to DHEA * Current smoker or pack year history \> 5 years (includes vaping/nicotine inhalation devices) * Positive urine cotinine test (\> 100 mg/mL) * Use of prednisone or antibiotics in the last 4 weeks * Use of any performance-enhancing drugs in the last 2 weeks * Use of DHEA in the last 2 weeks * Androgen use for any reason * HSD3B1 CC phenotype * Any other condition or finding that would compromise the safety of the subject or the quality of the study data, or otherwise interfere with achieving the study objectives, as determined by the PI * Menopausal amenorrhea by history * Positive PSA (\>4 ng/ml) (Prostate Specific Antigen) * Prior diagnosis of vocal cord dysfunction, bronchopulmonary dysplasia, cystic fibrosis, chronic obstructive pulmonary disorder, or other lung disease * Systolic blood pressure \> 150 mm Hg and/or diastolic blood pressure \>90 mm Hg * Heart rates outside the range of 50 to 120 beats per minutes or with a pathologic irregularity * Patients afflicted with any additional acute or chronic pathology that in the opinion of the screening physician makes them unsuitable for study or increases the risks associated with the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Peak DHEA Concentration ≥100ng/mL or < 100ng/mL at Any Time Point During Single or Multiple Dose Treatments. | Outcome measure assessed at 50mg Single Dose Visit (Day 14), 100mg Single Dose Visit (Day 22), 50mg Multiple Dose Treatment (Days 30-32), 100mg Multiple Dose Treatment (Days 40-42) | The objective is to determine the maximum tolerated dose of slow release DHEA in patients with asthma and AA or AC genotype by measuring the presence in and difference of pharmacokinetics of DHEA in the blood at two dose levels (50mg and 100mg). |
| Number of Participants With a Significant, Sustained Increase in DHEA-S in Blood Levels and Without a Significant, Sustained Increased in DHEA-S in Blood Levels for More Than 24hrs, During Multiple Dose Treatments. | Outcome measure assessed every 24 hours during 50mg Multiple Dose Treatment (Days 30-32) and every 24 hours during 100mg Multiple Dose Treatment (Days 40-42) | The objective is to determine the maximum tolerated dose of slow release DHEA in patients with asthma and AA or AC genotype by measuring the presence in and difference of pharmacokinetics of DHEA-S in the blood at two dose levels (50mg and 100mg). |
| Number of Participants With Adverse Events (AEs) Related to Study, Unlikely Related to Study, or no AEs at All, at Any Time Point During Single Dose Periods, Multiple Dose Periods, or Washout Periods. | From administration of the first dose to 12 hours after the final dose (up to 59 days) | The objective is to determine the maximum tolerated dose of slow release DHEA in patients with asthma and AA or AC genotype by evaluating the occurrences and severity of adverse events during or after dosing at two levels (5omg and 100mg). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Significant Change in Vital Sign Measurement and no Significant Change in Vital Sign Measurements After 50mg Single Dose and After 100mg Single Dose. | Outcome measure assessed at 50mg Single Dose Visit (Day 14) and 100mg Single Dose Visit (Day 22). | The objective is to evaluate the safety and tolerability of slow release DHEA in asthma by measuring the change in vital signs from before 50mg single dose treatment to after 50mg single dose treatment and from beginning of 100mg dose treatment to after 100mg dose treatment. |
| Number of Participants With Significant Change in Asthmatic Symptoms, or no Significant Change in Asthmatic Symptoms, After 50mg Multiple Dose and 100mg Multiple Dose. | Outcome measure assessed at 50mg Multiple Dose Treatment (Day 30), 100mg Multiple Dose Treatment (Day 40) | The objective is to evaluate the safety and tolerability of slow release DHEA in asthma by measuring the change in physical symptoms from before treatment to after treatment. Physical symptoms will include reports such as cough, shortness of breath, chest tightness, wheeze, as measured by symptom diary record. |
| Number of Participants With a Decrease in FEV1, an Increase in FEV1, and no Change in FEV1, After 50mg Multiple Dose Treatments and 100mg Multiple Dose Treatments. | Outcome measure assessed from beginning to end of 50mg Multiple Dose Treatment (Days 30-32), and beginning to end of 100mg Multiple Dose Treatment (Days 40-42) | The objective is to evaluate the safety and tolerability of slow release DHEA in asthma patients by performing pulmonary function testing to obtain measurements of FEV (forced expiratory volume) before treatment and after treatment. All subjects completed the treatment, but not all subjects participated in the pulmonary function testing. |
| Number of Participants That Experienced an Asthma Exacerbation and That Did Not Experience an Asthma Exacerbation During or After 50mg Single Dose, 100mg Single Dose, 50mg Multiple Dose Treatment, 100mg Multiple Dose Treatment. | Outcome measure assessed at 50mg Single Dose Visit (Day 14), 100mg Single Dose Visit (Day 22), 50mg Multiple Dose Treatment (Days 30-32), 100mg Multiple Dose Treatment (Days 40-42). | The objective is to evaluate the safety and tolerability of slow release DHEA in asthma patients by recording any instance of asthma exacerbation event during or after treatment. |
Countries
United States
Participant flow
Recruitment details
This is a crossover study; subjects who were enrolled into the 50mg arm completed that arm and a washout and then began the 100mg arm.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Region of Enrollment United States | 9 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 9 | 0 / 9 | 0 / 9 |
| other Total, other adverse events | 0 / 9 | 1 / 9 | 0 / 9 | 2 / 9 |
| serious Total, serious adverse events | 0 / 9 | 0 / 9 | 0 / 9 | 0 / 9 |
Outcome results
None listed